The long range goal of this project is to study the oxidation of chemicals to toxic metabolites by prostaglandin synthetase (PGS) and to demonstrate the significance of this system in chemical-induced toxicity or carcinogenesis. BP-7, 8-diol metabolism was studied in 10Tl/2 cells where the PG's and NADPH-dependent oxidation can be compared. Stimulation of PGS resulted in elevation of metabolism and higher cell transformation. These studies suggest a potentially important role for PGS in BP-induced cell transformation. In addition, we studied the metabolism of DES and acetoaminophen by PGS. Both chemicals are metabolized to reactive intermediates by PGS. The effect of a PGS inhibitor, aspirin on the development of BP-induced lung tumors in mice, is currently being studied.